The present work continues prior investigation of insulin receptors on circulating cells in patients with insulin resistance and diabetes mellitus. Insulin receptors are evaluated for their ability to bind insulin and to act as tyrosine-specific protein kinases. We have specifically studied two individual patients: one with a Type A form of insulin resistance that binds insulin normally but has reduced tyrosine- kinase activity, and the second, a patient with a Rabson-Mendenhall Syndrome, who has a severe defect in insulin binding. In addition, we have continued to study patients with autoantibodies to the insulin receptor associated with insulin resistance.